U.S. patent number 6,673,154 [Application Number 09/896,000] was granted by the patent office on 2004-01-06 for stent mounting device to coat a stent.
This patent grant is currently assigned to Advanced Cardiovascular Systems, Inc.. Invention is credited to Stephen D. Pacetti, Plaridel K. Villareal.
United States Patent |
6,673,154 |
Pacetti , et al. |
January 6, 2004 |
Stent mounting device to coat a stent
Abstract
A stent mounting device and a method of coating a stent using
the device are provided.
Inventors: |
Pacetti; Stephen D. (San Jose,
CA), Villareal; Plaridel K. (San Jose, CA) |
Assignee: |
Advanced Cardiovascular Systems,
Inc. (Santa Clara, CA)
|
Family
ID: |
29737289 |
Appl.
No.: |
09/896,000 |
Filed: |
June 28, 2001 |
Current U.S.
Class: |
118/500;
623/1.46 |
Current CPC
Class: |
B05B
13/0442 (20130101); B05D 1/002 (20130101) |
Current International
Class: |
B05B
13/02 (20060101); B05B 13/04 (20060101); B05D
1/00 (20060101); B05C 013/02 () |
Field of
Search: |
;118/500
;427/2.24,2.25,2.28,2.3 ;623/1.46,1.47,1.48 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Edwards; Laura
Attorney, Agent or Firm: Squire, Sanders & Dempsey,
L.L.P.
Claims
What is claimed is:
1. An apparatus for supporting a stent during a process of coating
the stent, comprising: a first member for making contact with a
first end of the stent aid a second member for making contact with
a second end of the stent, wherein a section of the first or second
member includes a porous surface capable of receiving a coating
substance during the coating process.
2. The apparatus of claim 1, wherein the first or second member is
made from a metallic material selected from the group consisting of
stainless steel, titanium, tantalum, niobium, zirconium, hafnium,
and cobalt chromium alloys.
3. The apparatus of claim 1, wherein the first or second member is
made from a polymeric material.
4. The apparatus of claim 3, wherein the polymeric material is
selected from the group consisting of regenerated cellulose,
cellulose acetate, polyacetal, polyetheretherketone, polyesters,
highly hydrolyzed polyvinyl alcohol, nylon, polyphenylenesulfide,
polyethylene, polyethylene terephthalate, polypropylene, and
combinations thereof.
5. The apparatus of claim 1, wherein the first or second member is
made from a ceramic material selected from the group consisting of
zirconia, silica glass, sintered calcium phosphates, calcium
sulfate, and titanium dioxide.
6. The apparatus of claim 1, wherein the first and second members
have inwardly tapered ends that penetrate at least partially in the
first and second ends of the stent and are in contact with the
first and second ends of the stent.
7. The apparats of claim 1, additionally comprising a third member
for extending within the stent and for securing the first member to
the second member.
8. The apparatus of claim 7, wherein the outer surface of the third
member does not make contact with the inner surface of the
stent.
9. A mounting assembly for supporting a stent during the
application of a coating composition onto the stent, comprising: a
support member including a first member for supporting a first end
of the stent and a second member for supporting a second end of the
stent, wherein the first or second member includes cavities for
receiving and containing excess coating composition applied to the
stent during the application process.
10. The mounting assembly of claim 9, wherein the support member
additionally includes a third member for extending within the stent
and/for securing the first member to the second member and wherein
the distance between the first member and the second member can be
adjusted by inserting the third member deeper into the first member
or the second member.
11. A mounting assembly for supporting a stent during the
application of a coating composition onto the stent, comprising: a
support member including a first member for supporting a first end
of the stent and a second member for supporting a second end of the
stent, and a layer disposed on the surface of the first or second
member to absorb coating composition that comes into contact with
the layer during the application process.
12. An apparatus for supporting a stent during a process of coating
the stent, comprising: a first member for supporting a first end of
the stent; a second member for supporting a second end of the
stent; and a third member extending through the stent and
connecting the first member to the second member, wherein the
surface of the third member includes pores for receiving a coating
substance that is applied to the stent during the process of
coating the stent.
13. The apparatus of claim 12, wherein the third member does not
contact the inner surface of the stent.
14. An apparatus for supporting a stent during a process of coating
the stent, comprising: a first member for supporting a first end of
the stent; a second member for supporting a second end of the
stent; and a third member extending through the stent and
connecting the first member to the second member, wherein the third
member includes an absorbing layer or is made from an absorbing
material for at least partially absorbing some of a composition
that is applied to the stent during the process of coating the
stent.
15. The apparatus of claim 14, wherein the third member does not
contact the inner surface of the stent.
16. An apparatus for supporting a stent during a process of coating
the stent with a substance, comprising: a member for supporting a
stent during the coating process, the member including a first
member for making contact with a first end of the stent and a
second member for making contact with a second end of the stent,
wherein the first or second member is made from an absorbing
material for at least partially absorbing the substance that comes
into contact with the first or second member during the process of
coating the stent.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a stent mounting device and a method of
coating a stent using the device.
2. Description of the Background
Blood vessel occlusions are commonly treated by mechanically
enhancing blood flow in the affected vessels, such as by employing
a stent. Stents act as scaffoldings, functioning to physically hold
open and, if desired, to expand the wall of the passageway.
Typically stents are capable of being compressed, so that they can
be inserted through small lumens via catheters, and then expanded
to a larger diameter once they are at the desired location.
Examples in the patent literature disclosing stents include U.S.
Pat. No. 4,733,665 issued to Palmaz, U.S. Pat. No. 4,800,882 issued
to Gianturco, and U.S. Pat. No. 4,886,062 issued to Wiktor.
FIG. 1 illustrates a conventional stent 10 formed from a plurality
of struts 12. The plurality of struts 12 are radially expandable
and interconnected by connecting elements 14 that are disposed
between adjacent struts 12, leaving lateral openings or gaps 16
between adjacent struts 12. Struts 12 and connecting elements 14
define a tubular stent body having an outer, tissue-contacting
surface and an inner surface.
Stents are used not only for mechanical intervention but also as
vehicles for providing biological therapy. Biological therapy can
be achieved by medicating the stents. Medicated stents provide for
the local administration of a therapeutic substance at the diseased
site. Local delivery of a therapeutic substance is a preferred
method of treatment because the substance is concentrated at a
specific site and thus smaller total levels of medication can be
administered in comparison to systemic dosages that often produce
adverse or even toxic side effects for the patient.
One method of medicating a stent involves the use of a polymeric
carrier coated onto the surface of the stent. A composition
including a solvent, a polymer dissolved in the solvent. and a
therapeutic substance dispersed in the blend is applied to the
stent by immersing the stent in the composition or by spraying the
composition onto the stent. The solvent is allowed to evaporate,
leaving on the stent strut surfaces a coating of the polymer and
the therapeutic substance impregnated in the polymer.
A shortcoming of the above-described method of medicating a stent
is the potential for coating defects. While some coating defects
can be minimized by adjusting the coating parameters, other defects
occur due to the nature of the interface between the stent and the
apparatus on which the stent is supported during the coating
process. A high degree of surface contact between the stent and the
supporting apparatus can provide regions in which the liquid
composition can flow, wick, and collect as the composition is
applied. As the solvent evaporates, the excess composition hardens
to form excess coating at and around the contact points between the
stent and the supporting apparatus. Upon the removal of the coated
stent from the supporting apparatus, the excess coating may stick
to the apparatus, thereby removing some of the coating from the
stent and leaving bare areas. Alternatively, the excess coating may
stick to the stent, thereby leaving excess coating as clumps or
pools on the struts or webbing between the struts.
Thus, it is desirable to minimize the potential for coating defects
generated by the interface between the stent and the apparatus
supporting the stent during the coating process. Accordingly, the
present invention provides for a device for supporting a stent
during the coating application process. The invention also provides
for a method of coating the stent supported by the device.
SUMMARY OF THE INVENTION
The present invention provides an apparatus for supporting a stent
during a process of coating the stent. The apparatus includes a
member for supporting a stent during the coating process, wherein a
section of the member includes a porous surface capable of
receiving the coating substance during the coating process. The
pores can have a diameter between about 0.2 microns and about 50
microns.
In one embodiment, the member includes a first member for making
contact with a first end of the stent and a second member for
making contact with a second end of the stent. In such an
embodiment, the pores can be located on at least a region of the
surface of the first or second members. The first or second member
can be made from a metallic material such as 300 Series stainless
steel, 400 Series stainless steel, titanium, tantalum, niobium,
zirconium, hafnium, and cobalt chromium alloys. The first or second
member can also be made from a polymeric material such as, but not
limited to, regenerated cellulose, cellulose acetate, polyacetal,
polyetheretherketone, polyesters, highly hydrolyzed polyvinyl
alcohol, nylon, polyphenylenesulfide, polyethylene, polyethylene
terephthalate, polypropylene, and combinations thereof. The first
or second member can also be made from ceramics such as, but not
limited to, zirconia, silica, glass, sintered calcium phosphates,
calcium sulfate, and titanium dioxide. In another embodiment, a
layer can be disposed on the surface of the first or second member
to absorb coating material that comes into contact with the
layer.
In one embodiment, the first and second members have inwardly
tapered ends that penetrate at least partially in the first and
second ends of the stent and are in contact with the first and
second ends of the stent. In another embodiment, the apparatus
additionally includes a third member for extending within the stent
and for securing the first member to the second member.
The present invention also provides a method of coating a stent.
The method includes positioning a stent on a mounting assembly,
wherein a section of the mounting assembly includes a porous
surface. The method additionally includes applying a coating
composition to the stent, wherein at least some of the coating
composition that overflows from the stent is received by the pores.
The act of applying a coating composition can include spraying the
composition onto the stent.
In one embodiment, the method also includes at least partially
expanding the stent prior to the act of applying. The method can
also include rotating the stent about the longitudinal axis of the
stent during the act of applying and/or moving the stent in a
linear direction along the longitudinal axis of the stent during
the act of applying.
Also provided is a support assembly for a stent. The support
assembly includes a member for supporting a stent, wherein the
member includes an absorbing layer for at least partially absorbing
some of the coating material that comes into contact with the
absorbing layer.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 illustrates a conventional stent.
FIG. 2A illustrates a mounting assembly for supporting a stent in
accordance with one embodiment of the present invention.
FIG. 2B illustrates an expanded view of the mounting assembly in
accordance with one embodiment of the present invention.
FIG. 3A illustrates the interface between the mounting assembly and
the stent.
FIG. 3B is a cross-sectional view of the interface between the
mounting assembly and the stent in FIG. 3A.
FIG. 4A illustrates a fluid on a solid substrate having a contact
angle .phi..sub.A ;
FIG. 4B illustrates a fluid on a solid substrate having a contact
angle .phi..sub.B ;
FIG. 5 illustrates an end view of a coning end portion having a
porous covering over the outer surface thereof.
DETAILED DESCRIPTION
Embodiments of the Mounting Assembly
Referring to FIG. 2A, a mounting assembly 18 for supporting stent
10 is illustrated to include a support member 20, a mandrel 22, and
a lock member 24. Support member 20 can connect to a motor 26A so
as to provide rotational motion about the longitudinal axis of
stent 10, as depicted by arrow 28, during the coating process.
Another motor 26B can also be provided for moving support member 20
in a linear direction, back and forth, along a rail 29. The type of
stent 10 is not of critical importance and can include radially
expandable stents and stent-grafts.
Referring to FIG. 2B, support member 20 includes a coning end
portion 30, tapering inwardly at an angle .phi..sub.1 of about
15.degree. to about 75.degree., more narrowly from about 30.degree.
to about 60.degree.. By way of example, angle .phi..sub.1 can be
about 45.degree.. In accordance with one embodiment, mandrel 22 can
be permanently affixed to coning end portion 30. Alternatively,
support member 20 can include a bore 32 for receiving a first end
34 of mandrel 22. First end 34 of mandrel 22 can be threaded to
screw into bore 32. Alternatively, a non-threaded first end 34 and
bore 32 combination can be employed such that first end 34 can be
press-fitted or friction-fitted within bore 32 to prevent movement
of stent 10 on mounting assembly 18. Bore 32 should be deep enough
so as to allow mandrel 22 to securely mate with support member 20.
The depth of bore 32 can also be over-extended so as to allow a
significant length of mandrel 22 to penetrate bore 32. This would
allow the length of mandrel 22 to be adjusted to accommodate stents
of various sizes. In commercial embodiments, support member 20 can
be disposable or capable of being cleaned after each use, for
example in a solvent or oxidizing bath. or by pyrolizing out any
absorbed coating materials via heating at high temperatures.
The outer diameter of mandrel 22 should be smaller than the inner
diameter of stent 10 so as to prevent the outer surface of mandrel
22 from making contact with the inner surface of stent 10. A
sufficient clearance between the outer surface of mandrel 22 and
the inner surface of stent 10 should be provided to prevent mandrel
22 from obstructing the pattern of the stent body during the
coating process. By way of example, the outer diameter of mandrel
22 can be from about 0.010 inches (0.254 mm) to about 0.017 inches
(0.432 mm) when stent 10 has an inner diameter of between about
0.025 inches (0.635 mm) and about 0.035 inches (0.889 mm).
Lock member 24 includes a coning end portion 36 having an inwardly
tapered angle .phi..sub.2. Angle .phi..sub.2 can be the same as or
different than the above-described angle .phi..sub.1. A second end
38 of mandrel 22 can be permanently affixed to lock member 24 if
end 34 is disengagable from support member 20. Alternatively, in
accordance with another embodiment, mandrel 22 can have a threaded
second end 38 for screwing into a bore 40 of lock member 24. Bore
40 can be of any suitable depth that would allow lock member 24 to
be incrementally moved closer to support member 20. Accordingly,
stents 10 of any length can be securely pinched between support and
lock members 20 and 24. In accordance with yet another embodiment,
a non-threaded second end 38 and bore 40 combination is employed
such that second end 38 can be press-fitted or friction-fitted
within bore 40. In commercial embodiments, lock member 24 can be
disposable or capable of being cleaned after each use.
Mounting assembly 18 supports stent 10 via coning end portions 30
and 36. FIGS. 3A and 3B illustrate the interface between coning end
portions 30 and 36 and each end of stent 10 so as to provide
minimal contact between stent 10 and mounting assembly 18. Opposing
forces exerted from support and lock members 20 and 24, for
securely pinching stent 10, should be sufficiently strong so as to
prevent any significant movement of stent 10 on mounting assembly
18. However, the exerted force should not compress stent 10 so as
to distort the body of stent 10. Over or under application of
support force can lead to coating defects, such as non-uniformity
of the coating thickness.
In addition to supporting stent 10 with minimal contact, coning end
portions 30 and 36 also function to reduce buildup of coating
materials at the stent 10-mounting assembly 18 interface. Coning
end portions 30 and 36 should be able to absorb the coating
substance applied to stent 10. Thus, excess coating substance is
absorbed into coning end portions 30 and 36 and drawn away from
stent 10 during the coating process, further minimizing the
potential for webbing and other coating defects at the interface
between stent 10 and mounting assembly 18.
In one embodiment, the particular material selected for coning end
portions 30 and 36 can be any material having a plurality of pores
44 suitable to receive or absorb the coating substance deposited
thereon during the coating process. Pores 44 can be interconnected.
Interconnected pore structures are also known as open pore systems
as opposed to closed pore systems in which pores 44 are isolated
from one another. Interconnected pores 44 provide a network for
moving and holding the coating substance, thus enabling coning end
portions 30 and 36 to hold a larger amount of the coating substance
than coning end portions 30 and 36 having discrete pores 44, each
with a fixed capacity for uptake of the substance. The diameter of
pores 44 can be from about 0.2 microns to about 50 microns, for
example about 1 micron.
Coning end portions 30 and 36 can be made of materials having a
porous body or porous surfaces. Such materials can include
ceramics, metals, and polymeric materials. In accordance with
another embodiment, support member 20, mandrel 22, and/or lock
member 24 can also be made to have a porous surface. Examples of
suitable ceramics include, but are not limited to, zirconia,
silica, glass, sintered calcium phosphates, calcium sulfate, and
titanium dioxide.
Examples of suitable metals include, but are not limited to, 300
Series stainless steel, 400 Series stainless steel, titanium,
tantalum, niobium, zirconium, hafnium, and cobalt chromium alloys.
Surfaces having pores 44 can be made, for example, by sintering
pre-formed metallic particles together to form porous blanks that
can then be machined to a suitable shape or by sintering metallic
particles together in a suitably-shaped mold. In alternative
embodiments, the metal can be etched or bead-blasted to form a
porous surface. Etching can be conducted by exposing the surface to
a laser discharge, such as that of an excimer laser, or to a
suitable chemical etchant.
Examples of suitable polymeric materials include, but are not
limited to, regenerated cellulose, cellulose acetate, polyacetal,
polyetheretherketone, polyesters, highly hydrolyzed polyvinyl
alcohol, nylon, polyphenylenesulfide, polyethylene, polyethylene
terephthalate, polypropylene, and combinations thereof. Methods of
making polymers having pores 44, such as by foaming, sintering
particles to form a porous block, and phase inversion processing,
are understood by one of ordinary skill in the art. The polymeric
material selected should not be capable of swelling, dissolving, or
adversely reacting with the coating substance.
In one suitable embodiment, the polymeric material from which the
components are made is selected to allow the coating substance to
have a high capillary permeation when a droplet of the coating
substance is placed thereon. Capillary permeation or wetting is the
movement of a fluid on a solid substrate driven by interfacial
energetics. Capillary permeation is quantitated by a contact angle,
defined as an angle at the tangent of a droplet in a fluid phase
that has taken an equilibrium shape on a solid surface. A low
contact angle indicates a higher wetting liquid. A suitably high
capillary permeation corresponds to a contact angle less than about
90.degree.. FIG. 4A illustrates a droplet 46 of the coating
substance on a flat, nonporous surface 48A composed of the same
material as coning end portion 30 or 36. Fluid droplet 46 has a
high capillary permeation that corresponds to a contact angle
.phi..sub.A, which is. less than about 90.degree.. By contrast,
FIG. 4B illustrates fluid droplet 46 on a surface 48B having a low
capillary permeation that corresponds to a contact angle
.phi..sub.B, which is greater than about 90.degree.. Surface
treatments understood by one of ordinary skill in the art, such as
plasma treating, corona treating, chemical oxidation, and etching,
can be used to modify the surface to render the surface more
capable of allowing the coating substance to have a suitably high
capillary permeation.
FIG. 5 illustrates an embodiment in which the outer surface of
coning end portions 30 and/or 36 is covered with a layer 50. In
such an embodiment, coning end portions 30 and/or 36 can have
either porous or non-porous surfaces, while layer 50 can be made of
an absorbent material, such as a sponge. Accordingly, layer 50 can
absorb excess coating substance flowing off of stent 10. In
addition, support member 20, mandrel 22, and/or lock member 24 can
also be covered with layer 50.
While the device of the present invention has been described herein
as having coning end portions 30 and 36 that support the respective
ends of a stent and draw excess coating materials away from the
stent via pores 44, it should be understood that the present
invention is not limited thereto. Rather, the stent mounting
assembly of the present invention can be any device that includes
porous regions for supporting a stent as well as for absorbing
excess coating materials to minimize coating defects.
Coating a Stent Using the Mounting Assembly
The following method of application is being provided by way of
illustration and is not intended to limit the embodiments of
mounting assembly 18 of the present invention. A spray apparatus,
such as EFD 780S spray device with VALVEMATE 7040 control system
(manufactured by EFD Inc., East Providence, R.I.), can be used to
apply a composition to a stent. EFD 780S spray device is an
air-assisted external mixing atomizer. The composition is atomized
into small droplets by air and uniformly applied to the stent
surfaces. The atomization pressure can be maintained at a range of
about 5 psi to about 20 psi. The droplet size depends on such
factors as viscosity of the solution, surface tension of the
solvent, and atomization pressure. Other types of spray
applicators, including air-assisted internal mixing atomizers and
ultrasonic applicators, can also be used for the application of the
composition.
During the application of the composition, a stent supported by
mounting assembly 18 can be rotated about the stent's central
longitudinal axis. Rotation of the stent can be from about 1 rpm to
about 300 rpm, more narrowly from about 50 rpm to about 150 rpm. By
way of example, the stent can rotate at about 120 rpm. The stent
can also be moved in a linear direction along the same axis. The
stent can be moved at about 1 mm/second to about 12 mm/second, for
example about 6 mm/second, or for a minimum of at least two passes
(i.e., back and forth past the spray nozzle). The flow rate of the
solution from the spray nozzle can be from about 0.01 mg/second to
about 1.0 mg/second, more narrowly about 0.1 mg/second. Multiple
repetitions for applying the composition can be performed, wherein
each repetition can be, for example, about 1 second to about 10
seconds in duration. The amount of coating applied by each
repetition can be about 0.1 micrograms/cm.sup.2 (of stent surface)
to about 40 micrograms/cm.sup.2, for example less than about 2
micrograms/cm.sup.2 per 5-second spray.
Each repetition can be followed by removal of a significant amount
of the solvent. Depending on the volatility of the particular
solvent employed, the solvent can evaporate essentially upon
contact with the stent. Alternatively, removal of the solvent can
be induced by baking the stent in an oven at a mild temperature
(e.g., 60.degree. C.) for a suitable duration of time (e.g., 2-4
hours) or by the application of warm air. The application of warm
air between each repetition prevents coating defects and minimizes
interaction between the active agent and the solvent. The
temperature of the warm air can be from about 30.degree. C. to
about 60.degree. C., more narrowly from about 40.degree. C. to
about 50.degree. C. The flow rate of the warm air can be from about
20 cubic feet/minute (CFM) (0.57 cubic meters/minute (CMM)) to
about 80 CFM (2.27 CMM), more narrowly about 30 CFM (0.85 CMM) to
about 40 CFM (1.13 CMM). The warm air can be applied for about 3
seconds to about 60 seconds, more narrowly for about 10 seconds to
about 20 seconds. By way of example, warm air applications can be
performed at a temperature of about 50.degree. C., at a flow rate
of about 40 CFM, and for about 10 seconds. Any suitable number of
repetitions of applying the composition followed by removing the
solvent(s) can be performed to form a coating of a desired
thickness or weight. Excessive application of the polymer in a
single application can, however, cause coating defects.
Operations such as wiping, centrifugation, or other web clearing
acts can also be performed to achieve a more uniform coating.
Briefly, wiping refers to the physical removal of excess coating
from the surface of the stent; and centrifugation refers to rapid
rotation of the stent about an axis of rotation. The excess coating
can also be vacuumed off of the surface of the stent.
In accordance with one embodiment, the stent can be at least
partially pre-expanded prior to the application of the composition.
For example, the stent can be radially expanded about 20% to about
60%, more narrowly about 27% to about 55% the measurement being
taken from the stent's inner diameter at an expanded position as
compared to the inner diameter at the unexpanded position. The
expansion of the stent, for increasing the interspace between the
stent struts during the application of the composition. can further
prevent "cob web" formation between the stent struts.
In accordance with one embodiment, the composition can include a
solvent and a polymer dissolved in the solvent. The composition can
also include active agents, radiopaque elements, or radioactive
isotopes. Representative examples of polymers that can be used to
coat a stent include ethylene vinyl alcohol copolymer (commonly
known by the generic name EVOH or by the trade name EVAL),
poly(hydroxyvalerate); poly(L-lactic acid); polycaprolactone;
poly(lactide-co-glycolide); poly(hydroxybutyrate);
poly(hydroxybutyrate-co-valerate); polydioxanone; polyorthoester;
polyanhydride; poly(glycolic acid); poly(D,L-lactic acid);
poly(glycolic acid-co-trimethylene carbonate); polyphosphoester;
polyphosphoester urethane; poly(amino acids); cyanoacrylates;
poly(trimethylene carbonate); poly(iminocarbonate);
copoly(ether-esters) (e.g. PEO/PLA); polyalkylene oxalates;
polyphosphazenes; biomolecules, such as fibrin, fibrinogen,
cellulose, starch, collagen and hyaluronic acid; polyurethanes;
silicones; polyesters; polyolefins; polyisobutylene and
ethylene-alphaolefin copolymers; acrylic polymers and copolymers;
vinyl halide polymers and copolymers, such as polyvinyl chloride;
polyvinyl ethers, such as polyvinyl methyl ether; polyvinylidene
halides, such as polyvinylidene fluoride and polyvinylidene
chloride; polyacrylonitrile; polyvinyl ketones; polyvinyl
aromatics, such as polystyrene; polyvinyl esters, such as polyvinyl
acetate; copolymers of vinyl monomers with each other and olefins,
such as ethylene-methyl methacrylate copolymers,
acrylonitrile-styrene copolymers, ABS resins, and ethylene-vinyl
acetate copolymers; polyamides, such as Nylon 66 and
polycaprolactam; alkyd resins; polycarbonates; polyoxymethylenes;
polyimides; polyethers; epoxy resins; polyurethanes; rayon;
rayon-triacetate; cellulose; cellulose acetate; cellulose butyrate;
cellulose acetate butyrate; cellophane; cellulose nitrate;
cellulose propionate; cellulose ethers; and carboxymethyl
cellulose.
"Solvent" is defined as a liquid substance or composition that is
compatible with the polymer and is capable of dissolving the
polymer at the concentration desired in the composition. Examples
of solvents include, but are not limited to, dimethylsulfoxide
(DMSO), chloroform, acetone, water (buffered saline), xylene,
methanol, ethanol, 1-propanol, tetrahydrofuran, 1-butanone,
dimethylformamide, dimethylacetamide, cyclohexanone, ethyl acetate,
methylethylketone, propylene glycol monomethylether, isopropanol,
isopropanol admixed with water, N-methyl pyrrolidinone, toluene,
and combinations thereof.
The active agent could be for inhibiting the activity of vascular
smooth muscle cells. More specifically, the active agent can be
aimed at inhibiting abnormal or inappropriate migration and/or
proliferation of smooth muscle cells for the inhibition of
restenosis. The active agent can also include any substance capable
of exerting a therapeutic or prophylactic effect in the practice of
the present invention. For example, the agent can be for enhancing
wound healing in a vascular site or improving the structural and
elastic properties of the vascular site. Examples of agents include
antiproliferative substances such as actinomycin D, or derivatives
and analogs thereof (manufactured by Sigma-Aldrich 1001 West Saint
Paul Avenue, Milwaukee, Wis. 53233; or COSMEGEN available from
Merck). Synonyms of actinomycin D include dactinomycin, actinomycin
IV, actinomycin I.sub.1, actinomycin X.sub.1, and actinomycin
C.sub.1. The active agent can also fall under the genus of
antineoplastic, antiinflammatory, antiplatelet, anticoagulant,
antifibrin, antithrombin, antimitotic, antibiotic, antiallergic and
antioxidant substances. Examples of such antineoplastics and/or
antimitotics include paclitaxel (e.g. TAXOL.RTM. by Bristol-Myers
Squibb Co., Stamford, Conn.), docetaxel (e.g. Taxotere.RTM., from
Aventis S.A., Frankfurt, Germany) methotrexate, azathioprine,
vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride
(e.g. Adriamycin.RTM. from Pharmacia & Upjohn, Peapack N.J.),
and mitomycin (e.g. Mutamycin.RTM. from Bristol-Myers Squibb Co.,
Stamford, Conn.) Examples of such antiplatelets, anticoagulants,
antifibrin, and antithrombins include sodium heparin, low molecular
weight heparins, heparinoids, hirudin, argatroban, forskolin,
vapiprost, prostacyclin and prostacyclin analogues, dextran,
D-phe-pro-arg-chloromethylketone (synthetic antithrombin),
dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor
antagonist antibody, recombinant hirudin, and thrombin inhibitors
such as Angiomax.TM. (Biogen, Inc., Cambridge, Mass.) Examples of
such cytostatic or antiproliferative agents include angiopeptin,
angiotensin converting enzyme inhibitors such as captopril (e.g.
Capoten.RTM. and Capozide.RTM. from Bristol-Myers Squibb Co.,
Stamford, Conn.), cilazapril or lisinopril (e.g. Prinivil.RTM. and
Prinzide.RTM. from Merck & Co., Inc., Whitehouse Station, NJ);
calcium chaninel blockers (such as nifedipine), colchicine,
fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty
acid), histamine antagonists, lovastatin (an inhibitor of HMG-CoA
reductase, a cholesterol lowering drug, brand name Mevacoro from
Merck & Co., Inc., Whitehouse Station, NJ), monoclonal
antibodies (such as those specific for Platelet-Derived Growth
Factor (PDGF) receptors), nitroprusside, phosphodiesterase
inhibitors, prostaglandin inhibitors, suramin, serotonin blockers,
steroids, thioprotease inhibitors, triazolopyrimidine (a PDGF
antagonist), and nitric oxide. An example of an antiallergic agent
is permirolast potassium. Other therapeutic substances or agents
which may be appropriate include alpha-interferon, genetically
engineered epithelial cells, rapamycin and dexamethasone. Exposure
of the active ingredient to the composition should not adversely
alter the active ingredient's composition or characteristic.
Accordingly, the particular active ingredient is selected for
compatibility with the solvent or blended polymer-solvent.
Examples of radiopaque elements include, but are not limited to,
gold, tantalum, and platinum. An example of a radioactive isotope
is P.sup.32. Sufficient amounts of such substances may be dispersed
in the composition such that the substances are not present in the
composition as agglomerates or flocs.
While particular embodiments of the present invention have been
shown and described, it will be obvious to those skilled in the art
that changes and modifications can be made without departing from
this invention in its broader aspects. Therefore, the appended
claims are to encompass within their scope all such changes and
modifications as fall within the true spirit and scope of this
invention.
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